The experimental program described in this proposal is designed to quantitate markers of Herpes simplex virus (HSV) infection in a human population already participating in an epidemiological study of cervical cancer. The patients and control groups are individuals involved in the study entitled "Case-control study of cervical cancer". The patients and control groups are individuals involved in the study entitled "Case-control study of invasive cervical cancer", funded by the National Cancer Institute, at present underway at the University of Colorado School of Medicine. As a collaborative endeavor, we plan to utilize blood from these individuals to assay for evidence of Herpes simplex virus infection and determine the extent of their immune responsiveness to viral antigens. The specific aims are: 1) To quantitate lymphocyte proliferation in response to inactivated HSV-1 and HSV-2 virus and a type specific glycoprotein (gC); 2) To examine circulating lymphocytes for the presence of viral DNA, measure the amount of DNA, and by use of specific probes establish whether the virus is type 1 or type 2; 3) To determine by an enzyme linked immunoassay, the serum antibody levels against total herpes virus antigens and the type specific glycoprotein gC; and 4) To utilize these techniques in persons with known HSV infections, and to incorporate these techniques into an on-going study of cervical cancer cases and controls. The quantitative data generated by the laboratory will first be developed using known HSV infected cell lines in in vitro experiments. Next, white cell material will be obtained from persons known to be infected with HSV-1 and HSV-2 from the sexually transmitted diseases clinic of Denver Health and Hospitals. This will serve to validate the findings, and help establish the sensitivity and specificity of the procedures. Next, and the principal focus of the collaborative portion of this proposal, white cell samples will be analyzed from persons already participating in the case-control study of cervical cancer. This will allow examination of the laboratory information on HSV experience simultaneously with epidemiologic information relevant to other potential etiologic and confounding factors, such as smoking, nutritional status, sexual and infectious disease history, and contraceptive and hormone useage patterns.